TY - JOUR
T1 - Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation
AU - Miyamoto, Chizuko
AU - Kojo, Satoshi
AU - Yamashita, Motoi
AU - Moro, Kazuyo
AU - Lacaud, Georges
AU - Shiroguchi, Katsuyuki
AU - Taniuchi, Ichiro
AU - Ebihara, Takashi
N1 - Funding Information:
We thank W.M. Yokoyama, D.K. Sojka, B. Plougastel-Douglas, and T. Egawa for helpful discussions, E. Park, M.D. Bern, J. Poursine-Laurent, L. Yang, and S.M. Taffner for technical assistance, and K. Takeda for the IL-10-Venus mice. This study was supported by the “Kibou Project 2016” Startup Support for Young Researchers in Immunology (T.E.), JSPS KAKENHI Grant Number 18H02647 (T.E.), Riken (Incentive Research Project, FY2017) (T.E.), Takeda Science Foundation (T.E.), Mochida Memorial Foundation for Medical and Pharmaceutical Research (T.E.), and Suzuken Memorial Foundation (T.E.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. However, the mechanisms regulating prolonged ILC2-mediated TH2 cytokine production under chronic inflammatory conditions are unclear. Here we show that, at homeostasis, Runx deficiency induces excessive ILC2 activation due to overly active GATA-3 functions. By contrast, during allergic inflammation, the absence of Runx impairs the ability of ILC2s to proliferate and produce effector TH2 cytokines and chemokines. Instead, functional deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s. Finally, these ‘exhausted-like’ ILC2s are unable to induce type 2 immune responses to repeated allergen exposures. Thus, Runx confers competence for sustained ILC2 activity at the mucosa, and contributes to allergic pathogenesis.
AB - Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. However, the mechanisms regulating prolonged ILC2-mediated TH2 cytokine production under chronic inflammatory conditions are unclear. Here we show that, at homeostasis, Runx deficiency induces excessive ILC2 activation due to overly active GATA-3 functions. By contrast, during allergic inflammation, the absence of Runx impairs the ability of ILC2s to proliferate and produce effector TH2 cytokines and chemokines. Instead, functional deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s. Finally, these ‘exhausted-like’ ILC2s are unable to induce type 2 immune responses to repeated allergen exposures. Thus, Runx confers competence for sustained ILC2 activity at the mucosa, and contributes to allergic pathogenesis.
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U2 - 10.1038/s41467-019-08365-0
DO - 10.1038/s41467-019-08365-0
M3 - Article
C2 - 30683858
AN - SCOPUS:85060521878
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 447
ER -